The present invention relates to methods of treating patients having susceptible viral infections, especially chronic hepatitis C infections by administering to said patient a therapeutically effective amount of a combination therapy of interferon-alfa and ribavirin for a time sufficient to lower HCV-RNA in association with a therapeutically effective amount of an antioxidant for a time sufficient to ameliorate ribavirin-related hemolysis.
A chronic hepatitis C viral infection is a particularly insidious and slow-progressing viral disease having a significant impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocellular carcinoma.
Combination treatment with interferon alfa-2b and ribavirin for chronic hepatitis C in patients, is disclosed by Reichard et al.(The Lancet 1998; 351;83-87. T. Poynard et al.(The Lancet, 1998, Vol. 352, October 31, p 1426-1432) disclose that treating chronic hepatitis C patients who had not been treated with interferon or ribavirin with 3 MIU of interferon alfa-2b TIW plus 1000-1200 mg of ribavirin per day for 48 weeks resulted in a sustained virological response at 24 weeks after treatment in 43% of the patients. See also J. G. McHutchinson et al. (N. Engl. J. Med., 1998, 339:1485-1492), G. L. Davis et al. (N. Engl. J. Med., 1998, 339:1493-1499) disclose that treating chronic hepatitis C patients who relapsed after treatment with interferon with 3 MIU of interferon alfa-2b TIW plus 100-1200 mg of ribavirin per day for 48 weeks results in higher rates of sustained virologic response than treatment with interferon alone.
However this combination therapy is not always effective due to side effects associated with ribavirin such as ribavirin-related hemolysis as measured by reduced hemoglobin concentrations. Both McHutchinson, et al and Poynard, et al report that the majority of patients who completed the combination therapy had reached their lowest hemoglobin concentration by the fourth week of combination therapy at which time the hemoglobin concentrations either stabilized or increased. Ribavirin dose reduction to 600 mg/day was reported by McHutchinson, et al for patients with hemoglobin concentrations below 10 g per deciliter and treatment with ribavirin was discontinued in patients with hemoglobin concentration below 8.5 g per deciliter.
There is a need to provide an improved combination therapy for treating susceptible viral infections, especially chronic hepatitis C patients, to ameloriate the ribavirin-related hemolysis throughout the duration of the combination especially in the first 4 to 12 weeks, of therapy so as to produce a sustained virological response in more patients than previously possible.